Managing motivational conflict: how self-esteem and executive resources influence self-regulatory responses to risk.
This article explores how self-esteem and executive resources interact to determine responses to motivational conflict. One correlational and 3 experimental studies investigated the hypothesis that high and low self-esteem people undertake different self-regulatory strategies in "risky" situations that afford opportunity to pursue competing goals and that carrying out these strategies requires executive resources. When such resources are available, high self-esteem people respond to risk by prioritizing and pursuing approach goals, whereas low self-esteem people prioritize avoidance goals. However, self-esteem does not influence responses to risk when executive resources are impaired. In these studies, risk was operationalized by exposing participants to a relationship threat (Studies 1 and 2), by using participants' self-reported marital conflict (Study 3), and by threatening academic competence (Study 4). Executive resources were operationalized as cognitive load (Studies 1 and 2), working memory capacity (Study 3), and resource depletion (Study 4). When executive resources were ample, high self-esteem people responded to interpersonal risk by making more positive relationship evaluations (Studies 1, 2, and 3) and making more risky social comparisons following a personal failure (Study 4) than did low self-esteem people. Self-esteem did not predict participants' responses when executive resources were impaired or when risk was absent. The regulatory function of self-esteem may be more resource-dependent than has been previously theorized.


Dosing quetiapine in drug-naive first-episode psychosis: a controlled, double-blind, randomized, single-center study investigating efficacy, tolerability, and safety of 200 mg/day vs. 400 mg/day of quetiapine fumarate in 141 patients aged 15 to 25 years.
To assess dosing, efficacy, and tolerability of quetiapine fumarate in drug-naive first-episode psychosis. We present a prospective, randomized, controlled, single-center, double-blind, fixed-dose, 4-week comparison study of 200 mg/day versus 400 mg/day of quetiapine in 141 drug-naive acutely ill first-episode psychosis patients (diagnosed according to DSM-IV) aged 15 to 25 years. The double-blind 4-week trial (Part 1) was followed by a single-blind, naturalistic, flexible-dose 8-week period (Part 2). The main outcome measures were symptomatic change, functioning, and tolerability. Data were collected from July 2003 until January 2006. The estimated time trends of the linear mixed-effects modeling indicated that efficacy between the 2 treatment groups in Part 1 was similar for most outcome measures except for 5 measures: the Scale for the Assessment of Negative Symptoms (SANS) anhedonia-asociality subscale (p = .011), the Social and Occupational Functioning Assessment Scale (p = .020), the Global Assessment of Functioning scale (p = .070), the SANS affective flattening or blunting subscale (p = .051), and the Udvalg for Kliniske Undersogelser total (p = .056), suggesting that the 200-mg group improved more for the SANS anhedonia-asociality subscale, whereas the 400-mg group showed a slight deterioration. Social and global functioning also improved more in the 200-mg group than in the 400-mg group. Part 2 of the study revealed that, independent of the initial target dose, when clinicians were able to adjust the dose flexibly, the dose at 12 weeks was similar between groups and averaged 268 mg/day. Our study in acutely ill drug-naive first-episode psychosis patients suggests that quetiapine is a safe and well-tolerated antipsychotic medication. In contrast to multiepisode patients, dosing should be more conservative in untreated new-onset cases. An initial dose of 250 to 300 mg/day of quetiapine is proposed as a primary target dose in drug-naive first-episode psychosis patients. clinicaltrials.gov Identifier: NCT00449397.


The structure of the C5a receptor-blocking domain of chemotaxis inhibitory protein of Staphylococcus aureus is related to a group of immune evasive molecules.
The chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) is a 121 residue excreted virulence factor. It acts by binding the C5a- (C5aR) and formylated peptide receptor (FPR) and thereby blocks specific phagocyte responses. Here, we report the solution structure of a CHIPS fragment consisting of residues 31-121 (CHIPS31-121). CHIPS31-121 has the same activity in blocking the C5aR compared to full-length CHIPS, but completely lacks FPR antagonism. CHIPS31-121 has a compact fold comprising an alpha-helix (residues 38-51) packed onto a four-stranded anti-parallel beta-sheet. Strands beta2 and beta3 are joined by a long loop with a relatively well-defined conformation. Comparison of CHIPS31-121 with known structures reveals striking homology with the C-terminal domain of staphylococcal superantigen-like proteins (SSLs) 5 and 7, and the staphyloccocal and streptococcal superantigens TSST-1 and SPE-C. Also, the recently reported structures of several domains of the staphylococcal extracellullar adherence protein (EAP) show a high degree of structural similarity with CHIPS. Most of the conserved residues in CHIPS and its structural homologues are present in the alpha-helix. A conserved arginine residue (R46 in CHIPS) appears to be involved in preservation of the structure. Site-directed mutagenesis of all positively charged residues in CHIPS31-121 reveals a major involvement of arginine 44 and lysine 95 in C5aR antagonism. The structure of CHIPS31-121 will be vital in the further unraveling of its precise mechanism of action. Its structural homology to S.aureus SSLs, superantigens, and EAP might help the design of future experiments towards an understanding of the relationship between structure and function of these proteins.


Axillary Reverse Mapping in Patients Undergoing Axillary Lymph Node Dissection: A Single Institution Experience From India.
Introduction Axillary lymph node dissection (ALND) remains the gold standard for clinically node-positive and sentinel node biopsy (SLNB) positive breast cancer patients, but it is associated with the debilitating morbidity of lymphedema. Recently, a new technique of axillary reverse mapping (ARM) has been described which helps in differentiating arm lymphatics from breast lymphatics. Aim To evaluate the applicability of the ARM technique with blue dye and the incidence of metastases in ARM nodes in the Indian population. Method A total of 120 patients underwent ARM during ALND. Blue lymphatic channels and lymph nodes were noted. All axillary nodes along with ARM nodes were dissected and sent separately for pathological evaluation for metastases. Results ARM nodes or lymphatics were identified in 65 (54.17%) out of 120 patients. The mean ARM lymph node yield was 1.4. The patients in whom ARM lymph nodes or lymphatics were not identified had significantly higher T stage and N stage (p <0.00001) than in whom it was identified. There was no significant correlation between ARM identification with BMI, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu), and neoadjuvant chemotherapy (NACT) status. ARM nodes were found metastatic in three patients (7.5%). All these patients had clinically N2 disease and all had pathologically more than ten nodes involved in the axilla. Conclusion The identification rate of ARM nodes and lymphatics with blue dye is lower in Indian patients who present with higher clinical T and N stage disease. Other clinicopathological parameters were not associated with the identification rate. The rate of metastasis in ARM nodes is high in patients with a high axillary tumor burden. Hence, preserving ARM nodes may not be oncologically safe in higher N stage disease.


Nitric oxide ameliorates hydrophobic bile acid-induced apoptosis in isolated rat hepatocytes by non-mitochondrial pathways.
Hydrophobic bile acids are toxic to isolated rat hepatocytes by mechanisms involving mitochondrial dysfunction and oxidative stress. In the current study we examined the role of nitric oxide (NO), a potential mediator of apoptosis, during bile acid-induced apoptosis. Freshly isolated rat hepatocytes and hepatic mitochondria generated NO and peroxynitrite (ONOO(-)) in a concentration- and time-dependent manner when exposed to the toxic bile salt glycochenodeoxycholate (GCDC) (25-500 microm), which was prevented by the nitric-oxide synthase (NOS) inhibitors N(G)-monomethyl-N-arginine monoacetate (l-NMMA) and 1400W. Relationships between hepatocyte NO production and apoptosis were examined by comparing the effects of NOS inhibitors with other inhibitors of GCDC-induced apoptosis. Inhibitors of caspases 8 and 9, the mitochondrial permeability transition blocker cyclosporin A, and the antioxidant idebenone reduced NO generation and apoptosis in GCDC-treated hepatocytes. In contrast, NOS inhibitors had no effect on GCDC-induced apoptosis despite marked reduction of NO and ONOO(-). However, treatment with the NO donors S-nitroso-N-acetylpenicillamine and spermine NONOate [N-(-aminoethyl)N-(2-hydroxy-2-nitrohydrazino)-1,2-ethylenediamine) inhibited apoptosis and caspase 3 activity while significantly elevating NO levels above GCDC-stimulated levels. Neither NO donors nor NOS inhibitors affected GCDC-induced mitochondrial permeability transition or cytochrome c release from liver mitochondria or GCDC-induced mitochondrial depolarization from isolated hepatocytes, suggesting that NO inhibits bile acid-induced hepatocyte apoptosis by a non-mitochondrial-dependent pathway. In conclusion, whereas NO produced from GCDC-treated hepatocytes neither mediates nor protects against bile acid-induced apoptosis, higher levels of NO inhibit GCDC-induced hepatocyte apoptosis by caspase-dependent pathways.


Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease.
We postulate that severe atherosclerotic occlusion of the circle of Willis and leptomeningeal arteries is an important factor in the pathogenesis of some sporadic Alzheimer's disease (AD) cases. These arterial stenoses are complicated by an overwhelming amyloid accumulation in the walls of leptomeningeal and cortical arteries resulting in a significant decrease in perfusion pressure and consequent ischemia/hypoxia of the brain tissue. We also propose that the distal areas of the white matter (WM) will be the first affected by a lack of oxygen and nutrients. Our hypotheses are supported by the following observations: (1) the number of stenoses is more frequent in AD than in the control population (p = 0.008); (2) the average index of occlusion is greater in AD than in the control group (p < 0.00001); (3) the index of stenosis and the total number of stenoses per case are positively correlated (R = 0.67); (4) the index of stenosis correlates with the neuropathological lesions of AD and with the MMSE psychometric test; (5) the number and degree of atherosclerosis of the anterior, middle and posterior cerebral arteries is more severe in cases of AD than in the control population; (6) atherosclerosis severity is apparently associated with the severity of the vascular amyloidosis; (7) the WM rarefaction correlates with the severity of the atherosclerosis and vascular amyloidosis; (8) the total cell count and microvessel count in the areas of WM rarefaction correlate with the neuropathological lesions of AD and with the MMSE score. Our data strongly suggest that severe hemodynamic disturbances contribute to sporadic AD and support the numerous observations indicating cardiovascular system participation in the pathogenesis of these dementias.


Determination of oxygen content in magnesium and its alloys by inert gas fusion-infrared absorptiometry.
A method for the determination of the oxygen content in magnesium and magnesium alloys has been developed. Inert gas fusion-infrared absorptiometry was modified by introducing a multistep heating process; a sample containing oxygen is fused with tin to form an eutectic mixture at 900°C in a graphite crucible, followed by a subsequent gradual temperature increase of up to 2000°C, which enables the evaporation of magnesium from the mixture, and subsequent solidification at the rim of the crucible. Residual tin including magnesium oxide remained at the bottom of the crucible. The oxygen in the tin is measured by a conventional inert gas fusion (IGF) method. From a comparison with the results of charged particle activation analysis, the IGF method is considered to be an attractive candidate for measuring the oxygen content in Mg and its alloys.


Parameter estimation in stochastic biochemical reactions.
Gene regulatory, signal transduction and metabolic networks are major areas of interest in the newly emerging field of systems biology. In living cells, stochastic dynamics play an important role; however, the kinetic parameters of biochemical reactions necessary for modelling these processes are often not accessible directly through experiments. The problem of estimating stochastic reaction constants from molecule count data measured, with error, at discrete time points is considered. For modelling the system, a hidden Markov process is used, where the hidden states are the true molecule counts, and the transitions between those states correspond to reaction events following collisions of molecules. Two different algorithms are proposed for estimating the unknown model parameters. The first is an approximate maximum likelihood method that gives good estimates of the reaction parameters in systems with few possible reactions in each sampling interval. The second algorithm, treating the data as exact measurements, approximates the number of reactions in each sampling interval by solving a simple linear equation. Maximising the likelihood based on these approximations can provide good results, even in complex reaction systems.


Differential effects of training intertrial interval on acquisition of trace and long-delay fear conditioning in rats.
Many factors govern conditioning effectiveness, including the intertrial interval (ITI) used during training. The present study systematically varied the training ITI during both trace and long-delay fear conditioning. Rats were trained using one of six different ITIs and subsequently tested for conditioning to the white noise conditioned stimulus (CS) and the training context. After trace conditioning, percent freezing to the CS was positively correlated with training ITI, whereas percent freezing to the context was negatively correlated with training ITI. In contrast, when rats were trained using a long-delay paradigm, freezing during the CS test session did not vary as a function of training ITI; rats exhibited robust freezing at all ITIs. The long-delay conditioned rats exhibited relatively low levels of freezing during the context test. Thus, trace is more sensitive than long-delay fear conditioning to variations in the training ITI. These data suggest that training ITI is an important variable to consider when evaluating age or treatment effects, where the optimal ITI may vary with advancing age or pharmacological treatment.


Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis.
Endometriosis is one of the most common reproductive system diseases, but the mechanisms of disease progression are still unclear. Due to its high recurrence rate, searching for potential therapeutic biomarkers involved in the pathogenesis of endometriosis is an urgent issue. Due to the similarities between endometriosis and ovarian cancer, four endometriosis datasets and one ovarian cancer dataset were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, followed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) analyses. Then, we validated gene expression and performed survival analysis with ovarian serous cystadenocarcinoma (OV) datasets in TCGA/GTEx database, and searched for potential drugs in the Drug-Gene Interaction Database. Finally, we explored the miRNAs of key genes to find biomarkers associated with the recurrence of endometriosis. In total, 104 DEGs were identified in the endometriosis datasets, and the main enriched GO functions included cell adhesion, extracellular exosome and actin binding. Fifty DEGs were identified between endometriosis and ovarian cancer datasets including 11 consistently regulated genes, and nine DEGs with significant expression in TCGA/GTEx. Only IGHM had both significant expression and an association with survival, three module DEGs and two significantly expressed DEGs had drug associations, and 10 DEGs had druggability. ITGA7, ITGBL1 and SORBS1 may help us understand the invasive nature of endometriosis, and IGHM might be related to recurrence; moreover, these genes all may be potential therapeutic targets.KEY MESSAGEThis manuscript used a bioinformatics approach to find target genes for the treatment of endometriosis.This manuscript used a new approach to find target genes by drawing on common characteristics between ovarian cancer and endometriosis.We screened relevant therapeutic agents for target genes in the drug database, and performed histological validation of target genes with both expression and survival analysis difference in cancer databases.


Fedotozine reversal of peritoneal-irritation-induced ileus in rats: possible peripheral action on sensory afferents.
Two kappa agonists, fedotozine and trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolydinyl)-cyclohexyl ]- benzeneacetamide methanesulfonate [(+/-)U-50,488H] were used to reverse the gastrointestinal transit inhibition induced by either peritoneal irritation (PI) or intracisternal (i.c.) administration of corticotropin releasing factor (CRF). PI was induced by acetic acid given i.p. Gastric emptying and intestinal transit were estimated with a 51Cr-labeled test meal. PI inhibited both gastric emptying (-50.9%) and intestinal transit (-48.8%). These inhibitions were prevented in a dose-dependent manner by the CRF antagonist, alpha-helical-CRF9-41 at doses (1-10 nmol/rat i.c.) that had no effect in control animals. CRF (300 pmol/rat i.c.) reproduced the gastrointestinal transit inhibitions seen under PI. The CRF effects were blocked by alpha-helical-CRF9-41 (10 nmol/rat) given i.c. but not i.v. Fedotozine (1-10 mg/kg s.c. but not 300 micrograms/rat i.c.v. or intrathecally) and (+/-)U-50,488H (0.3-3 mg/kg s.c. but not 100 micrograms/kg i.c.v.) reversed PI- but not CRF-induced ileus. Neither PI-induced ileus nor the fedotozine response was affected by perivagal capsaicin treatment. It was concluded that the PI-induced ileus depends on central CRF receptors. This result is consistent with the activation of an extrinsic inhibitory reflex. The reversal by kappa agonists of PI- but not CRF-induced ileus suggests that kappa agonists do not act after but before the CRF receptors. A possible peripheral action on nonvagal sensory afferents is suggested.


Insulin Does Not Target CamkIIα Neurones to Critically Regulate the Neuroendocrine Reproductive Axis in Mice.
Insulin signalling in the brain plays an important role in the central regulation of energy homeostasis and fertility, such that mice exhibiting widespread deletion of insulin receptors (InsR) throughout the brain and peripheral nervous system display diet sensitive obesity and hypothalamic hypogonadism. However, the specific cell types mediating the central effects of insulin on fertility remain largely unidentified. To date, the targeted deletion of InsR from individual neuronal populations implicated in the metabolic control of fertility has failed to recapitulate the hypogonadic and subfertile phenotype observed in brain-specific InsR knockout mice. Because insulin and leptin share similar roles as centrally-acting metabolic regulators of fertility, we used the Cre-loxP system to generate mice with a selective inactivation of the Insr gene from the same widespread neuronal population previously shown to mediate the central effects of leptin on fertility by crossing Insr-flox mice with calcium/calmodulin-dependent protein kinase type IIα (CamkIIα)-Cre mice. Multiple reproductive and metabolic parameters were then compared between male and female Insr-flox/Cre-positive (CamK-IRKO) and Insr-flox/Cre-negative control mice. Consistent with brain-specific InsR knockout mice, CamK-IRKO mice exhibited a mild but significant obesogenic phenotype. Unexpectedly, CamK-IRKO mice exhibited normal reproductive maturation and function compared to controls. No differences in the age of puberty onset, oestrous cyclicity or fecundity were observed between CamK-IRKO and control mice. We conclude that the central effects of insulin on the neuroendocrine reproductive axis are not critically mediated via the same neuronal populations targeted by leptin.


Statistical model based shape prediction from a combination of direct observations and various surrogates: application to orthopaedic research.
In computer-assisted orthopaedic surgery, recovering three-dimensional patient-specific anatomy from incomplete information has been focus of interest due to several factors such as less invasive surgical procedures, reduced radiation doses, and rapid intra-operative updates of the anatomy. The aim of this paper is to report results obtained combining statistical shape modeling and multivariate regression techniques for predicting bone shape from clinically and surgically relevant predictors, including sparse observations of the bone surface but also morphometric and anthropometric information. Different state of the art methods such as partial least square regression, principal component regression, canonical correlation analysis, and non-parametric kernel-based regression are compared. Clinically relevant surrogate variables and combinations are investigated on a database of 142 femur and 154 tibia shapes obtained from CT images. The results are evaluated using cross validation to quantify the prediction error. The proposed approach enables to characterize the added value of different predictors in a quantitative and localized fashion. Results indicate that complementary sources of information can be efficiently exploited to improve the accuracy of shape prediction.


Update on Total Pancreatectomy With Islet Autotransplantation.
Total pancreatectomy with islet autotransplantation is a therapeutic option to effectively achieve pain relief and improvements in quality of life for selected patients with debilitating pain from chronic pancreatitis. The understanding of the best application and clinical execution of this procedure is in evolution, with outcomes studies and clinical trials in progress.


Cartilage-hair hypoplasia associated with isolated hypoganglionosis: A case report.
Cartilage-hair hypoplasia is a rare metaphyseal chondrodysplasia characterized by diverse clinical manifestations and a high incidence of Hirschsprung disease. We present a male patient with cartilage-hair hypoplasia associated with severe intestinal obstruction. Genetic analysis of ribonuclease mitochondrial RNA-processing complex gene identified compound heterozygous mutations consisted with previously reported mutations: n.-14_3dupGAAGCTGAGGACGTGGT and n.183G > T. First, we considered that intestinal obstruction was due to an extensive type of Hirschsprung disease, but it was later confirmed as isolated hypoganglionosis. Isolated hypoganglionosis is rare and its therapeutic strategies are not well established. In cases of cartilage-hair hypoplasia associated with severe intestinal obstruction, the differential diagnosis of not only Hirschsprung disease, but also isolated hypoganglionosis, should be considered.


Preclinical studies of recombinant factor IX.
Recombinant factor IX (rFIX) has been extensively evaluated in preclinical studies. Dog model study of hemophilia B indicated that rFIX was as effective as a highly purified plasma-derived replacement factor in normalizing indices of hemostasis. Pharmacokinetic studies indicated a dose-proportional profile for rFIX. Pharmacokinetic/pharmacodynamic analysis showed that increases in the plasma concentration of rFIX following administration were closely correlated with measured factor IX activity in the plasma. Appropriate in vitro and in vivo toxicology studies have been performed to support the clinical use of rFIX for the treatment of hemophilia B. Finally, experiments in a model of thrombogenicity indicated that in animals rFIX has a low thrombogenic potential. The preclinical results provided a basis for proceeding with human clinical trials.


Preclinical pharmacology of Ro 31-6930, a new potassium channel opener.
The present study compares the effects of Ro 31-6930, a novel potassium channel opener, with those of cromakalim and nitrendipine on blood pressure and other haemodynamic parameters. In conscious, spontaneously hypertensive rats (SHR) the oral dose of Ro 31-6930 for lowering blood pressure was 10 times lower than that of cromakalim and some 100 times lower than that of nitrendipine. In addition, the duration of antihypertensive activity of Ro 31-6930 was longer than that of cromakalim or nitrendipine. The tachycardia evoked by Ro 31-6930 and cromakalim was of shorter duration than the antihypertensive effect of either agent. In a repeat, once daily dosing experiment no tolerance was observed to the antihypertensive effect of Ro 31-6930 over a 22-day period. In conscious normotensive cats Ro 31-6930 was 10 times more potent than cromakalim and 1,000 times more potent than nitrendipine in reducing blood pressure. The duration of hypotensive activity was in excess of 5 h for each agent. In anaesthetised dogs all three agents reduced mean arterial pressure (MAP) and total peripheral resistance (TPR), while increasing cardiac output (CO) via a rise in stroke volume (SV). Both Ro 31-6930 and cromakalim significantly reduced femoral (FVR) and mesenteric vascular resistances (MVR), while only cromakalim reduced renal vascular resistance (RVR). Ro 31-6930 is a potent new antihypertensive agent that compares favourably with cromakalim and nitrendipine.


The interstitial origin of germinal cells in the testis of the stickleback.
The brook stickleback, Culaea inconstans (Kirtland), in common with other bony fishes, lacks a germinal epithelium in the tubules of the testis, and the tubule wall is composed of a thin, discontinuous layer of myoid cells and collagenous fibers. Labelling of germ cells with tritiated thymidine has shown that the germ cells are derived from clumps of spermatogonia in the interstitial area. Large companion cells within the lumina of the tubules extend their processes to engulf spermatogonia from the interstitium which then enter the lumen of the tubule. Subsequent development of the germ cells takes place within individual compartments formed by folds of the plasma membrane of a companion cell. The companion cell, together with its complement of germ cells, constitutes a cyst. A companion cell may surround spermatogonia in the interstitium and at the same time encompass residual sperm of the previous season within the lumen. The plasma membranes of the germ cells and the companion cells remain discrete. Mature sperm are released into the lumen of the tubule and the companion cell again extends its processes into the interstitium and engulfs more spermatogonia for the following year. Companion cells may be homologous to the Sertoli cells of higher vertebrates although their processes penetrate the interstitium during the initial stages of spermatogenesis and they do not contain a permanent stock of spermatogonia.


WHY ARE THERE SO MANY SPECIES OF BROODING ANTARCTIC ECHINOIDS?
Marine invertebrates display a great variety of life-history traits and reproductive strategies. In echinoids, four patterns of larval development are generally recognized: planktotrophy, pelagic lecithotrophy, bottom dwelling, and brood protecting. Each broad type of free and protected development is found in all the oceans, but comparisons of the principal reproductive modes between different geographic regions have shown that they are not equally distributed. Frequency of pelagic development (planktotrophic and lecithotrophic) decreases from equator to Antarctic, where brood protecting becomes dominant. Numerous theories have been proposed to explain the richness of nonpelagic development in most marine invertebrates within the Southern Ocean. These theories can be grouped into three categories: (1) larval survival, where selection acts on larval; (2) energy allocation; and (3) dispersal. All of them consider the adaptative significance of brood protecting as the key to the success of this strategy in the Antarctic. However, the adaptative significance of brooding and the evolutionary success of this strategy in the Antarctic must be considered as two separate questions. To consider the problem at an evolutionary level, we have examined the consequences of different reproductive strategies on the genetic structure of species and on the long-term evolution of the clade. We examine this problem in the case of echinoids, a clade particularly well suited to addressing this question. In echinoids, the reduction of larval-stage duration is associated with a decrease in gene flow and consequently in the geographical scale of genetic differentiation. This allows us to reconsider the high-speciation-rate model, which leads to an increase in the number of low-dispersal species (isolation by distance). This model, previously tested by means of fossils is not satisfactory in living echinoids. Thus, the model is rebuilt with the addition of differential extinction rate between planktotrophic and brooding species in relation with the climatic history of the Antarctic.


Epsilon BP, a beta-galactoside-binding animal lectin, recognizes IgE receptor (Fc epsilon RI) and activates mast cells.
IgE-binding protein (epsilon BP) was originally identified in rat basophilic leukemia (RBL) cells by virtue of its affinity for IgE. epsilon BP is now known to be a beta-galactoside-binding lectin containing an S-type carbohydrate recognition domain. It is identical to a macrophage surface antigen, Mac-2, and lectins designated as CBP35, L-34, and RL-29, for which various functions have been suggested. Studies from other groups as well as ours have indicated that epsilon BP is secreted by cells such as macrophages and is present in extracellular fluids. We demonstrated previously that binding sites for epsilon BP are present on the surface of RBL cells. In this report, we show that epsilon BP binds to a small number of glycoprotein species on the surface of RBL cells. Significantly, one of these glycoproteins is the high-affinity IgE receptor (Fc epsilon RI). Preliminary studies showed that epsilon BP causes mediator release from RBL cells, possibly through cross-linking of Fc epsilon RI. The results suggest a function of epsilon BP as an activator of mast cells.


The exocyst is required for photoreceptor ciliogenesis and retinal development.
We previously have shown that the highly conserved eight-protein exocyst trafficking complex is required for ciliogenesis in kidney tubule cells. We hypothesized here that ciliogenic programs are conserved across organs and species. To determine whether renal primary ciliogenic programs are conserved in the eye, and to characterize the function and mechanisms by which the exocyst regulates eye development in zebrafish, we focused on exoc5, a central component of the exocyst complex, by analyzing both exoc5 zebrafish mutants, and photoreceptor-specific Exoc5 knock-out mice. Two separate exoc5 mutant zebrafish lines phenocopied exoc5 morphants and, strikingly, exhibited a virtual absence of photoreceptors, along with abnormal retinal development and cell death. Because the zebrafish mutant was a global knockout, we also observed defects in several ciliated organs, including the brain (hydrocephalus), heart (cardiac edema), and kidney (disordered and shorter cilia). exoc5 knockout increased phosphorylation of the regulatory protein Mob1, consistent with Hippo pathway activation. exoc5 mutant zebrafish rescue with human EXOC5 mRNA completely reversed the mutant phenotype. We accomplished photoreceptor-specific knockout of Exoc5 with our Exoc5 fl/fl mouse line crossed with a rhodopsin-Cre driver line. In Exoc5 photoreceptor-specific knock-out mice, the photoreceptor outer segment structure was severely impaired at 4 weeks of age, although a full-field electroretinogram indicated a visual response was still present. However, by 6 weeks, visual responses were eliminated. In summary, we show that ciliogenesis programs are conserved in the kidneys and eyes of zebrafish and mice and that the exocyst is necessary for photoreceptor ciliogenesis and retinal development, most likely by trafficking cilia and outer-segment proteins.


Erythema nodosum and glatiramer acetate treatment in relapsing-remitting multiple sclerosis.
Glatiramer acetate (GA), a well tolerated immunomodulatory treatment for relapsing-remitting multiple sclerosis (RR-MS), consists of a 4-amino acid polymer that mimics the myelin basic protein (MBP). We report the first case of biopsy-proven erythema nodosum (EN) in a patient presenting RR-MS under GA treatment. Comprehensive exams were negative in the search of the etiology of EN, which spontaneously resolved despite treatment continuation. GA treatment is known to generate reactive polyclonal antibodies that can cross-react with myelin epitopes, like MBP. These antibodies may also be implicated in allergenic reactions and auto-immune adverse events, such as anaphylactic shock, lymphadenopathy, livedo-like dermatitis, or lymphocytic infiltration. EN is an unspecific skin reaction occurring in several disorders and induced by many treatments. As EN can result from a polyclonal antibody response or type I hypersensitivity mechanisms, we hypothesize that GA treatment could be responsible for the occurrence of EN.


Assessment of growth performance and meat quality of finishing pigs raised on the low plane of nutrition.
This study was performed to investigate the effects of the low plane of nutrition on growth and meat quality of finishing pigs. A total of 136 crossbred barrows and gilts weighing approximately 55 kg were allotted to 8 pens, with 17 animals housed per pen, in a 2 (sex) × 2 (nutrition) factorial arrangement of treatments. The animals allotted to a medium plane of nutrition (MPN) received a finisher phase 1 (P1) diet containing 3.47 Mcal DE/kg and 0.92 % lysine and a P2 diet containing 3.40 Mcal DE/kg and 0.78 % lysine for 35 d and 36/43 d, respectively; the animals allotted to the low plane of nutrition (LPN) received only a P2 diet containing 3.00 Mcal DE/kg and 0.68 % lysine 7 d longer than MPN. The animals were slaughtered following the feeding trial, after which the loin, ham, Boston butt, and belly were taken from a total of 24 animals, with the average live weight being 120 kg, and their physicochemical and sensory quality traits were analyzed. Average daily gain did not differ between MPN and LPN during either P1 or P2. Average daily feed intake was greater (P < 0.05) in LPN vs. MPN during both phases whereas the opposite was true for the gain:feed ratio. Backfat thickness (BFT) was less in LPN vs. MPN (21.7 vs. 24.1 mm at 115 kg). The plane of nutrition influenced no effect on any of the physicochemical characteristics of fresh loin, ham, or Boston butt analyzed in the present study. Fresh hams from LPN exhibited superior aroma and odor scores than those from MPN; however, sensory quality traits were not influenced by the plane of nutrition in other fresh primal cuts or cooked meat. Instead, fresh primal cuts and cooked meat from gilts rendered superior physicochemical characteristics and sensory scores, respectively, than those from barrows. Results suggest that the low plane of nutrition may be useful to increase the slaughter weight of finishing pigs with a moderately high BFT by virtue of its BFT-lowering effect with or without exerting a slightly positive influence on pork quality.


Transfer of allergen-specific IgE-mediated hypersensitivity with allogeneic bone marrow transplantation.
We investigated whether allergen-specific IgE-mediated hypersensitivity is transferred by bone marrow transplantation. Twelve patients, 14 to 47 years of age, undergoing allogeneic bone marrow transplantation for the treatment of hematologic cancer were selected, along with their donors, by a screening questionnaire for a history of atopy in the donor. We evaluated these donor-recipient pairs before transplantation and at several points afterward for immediate skin-test reactivity to 17 allergens. For allergens for which pretransplantation skin tests had been positive in the donors and negative in the recipients, 20 of 46 post-transplantation skin tests were positive in 8 of the 11 recipients who survived for more than one year after transplantation. For allergens for which both donors and recipients had had negative skin tests before transplantation, only 6 of 256 tests (2.3 percent) were positive in the recipients after transplantation. Long-term transfer of donor-derived mite-specific IgE was demonstrated by radioallergosorbent testing in two recipients. Seven recipients either acquired or had an exacerbation of allergic rhinitis, and two recipients without a history of asthma had asthma one year after transplantation. We conclude that allergen-specific IgE-mediated hypersensitivity is adoptively transferred by bone marrow transplantation from donor to recipient by B cells with allergen-specific memory.


Coral reefs as the first line of defense: Shoreline protection in face of climate change.
Coral reefs are responsible for a wide array of ecosystem services including shoreline protection. However, the processes involved in delivering this particular service have not been fully understood. The objective of the present review was to compile the main results in the literature regarding the study of shoreline protection delivered by coral reefs, identifying the main threats climate change imposes to the service, and discuss mitigation and recovery strategies that can and have been applied to these ecosystems. While different zones of a reef have been associated with different levels of wave energy and wave height attenuation, more information is still needed regarding the capacity of different reef morphologies to deliver shoreline protection. Moreover, the synergy between the main threats imposed by climate change to coral reefs has also not been thoroughly investigated. Recovery strategies are being tested and while there are numerous mitigation options, the challenge remains as to how to implement them and monitor their efficacy.


EVALUATION OF THE THERAPEUTIC EFFICACY OF LEVAMISOLE HYDROCHLORIDE ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN EXPERIMENTALLY INFECTED MICE.
Lagochilascariosis, a disease caused by Lagochilascaris minor, affects the neck, sinuses, tonsils, lungs, the sacral region, dental alveoli, eyeballs and the central nervous system of humans. A cycle of autoinfection may occur in human host tissues characterized by the presence of eggs, larvae and adult worms. This peculiarity of the cycle hinders therapy, since there are no drugs that exhibit ovicidal, larvicidal and vermicidal activity. Given these facts, we studied the action of levamisole hydrochloride on third-stage larvae in the migration phase (G1) and on encysted larvae (G3) of L. minor. To this end, 87 inbred mice of the C57BL/6 strain were divided into test groups comprising 67 animals (G1-37; G3-30) and a control group (G2-10; G4-10) with 20 animals. Each animal was inoculated orally with 2,000 infective eggs of the parasite. The animals of the test groups were treated individually with a single oral dose of levamisole hydrochloride at a concentration of 0.075 mg. The drug was administered either 30 minutes prior to the parasite inoculation (G1 animals) or 120 days after the inoculation (G3 animals). The mice in the control groups were not treated with the drug. After the time required for the migration and the encysting of L. minor larvae, all the animals were euthanized and their tissues examined. The data were analyzed using the Student's unpaired t-test and the Levene test. The groups showed no statistically significant difference. Levamisole hydrochloride was ineffective on third-stage larvae of L. minor. These findings explain the massive expulsion of live adult worms, as well as the use of long treatment schemes, owing to the persistence of larvae and eggs in human parasitic lesions.


Answering Our Nation's Call: A Solution for Military Neurosurgery Wartime Readiness Through Civilian Collaboration.
Military-civilian partnerships have built the foundation for US neurosurgery as we see it today. Each conflict throughout history has led to expansion within the field of neurosurgery, benefiting civilian patients and those in uniform. Despite the field's growth during wartime, military neurosurgical case volume declines during peacetime, and as a result, important knowledge gained is at risk of being lost. The current landscape of military neurosurgery reflects the relative peacetime for the US-World relationship. Because of this peacetime, the surgical case volume and experience of the military neurosurgeon are declining rapidly. In addition to providing a history of military-civilian partnerships in neurosurgery, we have analyzed the declining case volume trends at a single military treatment facility with neurosurgical capabilities. We compared the case volume of a military neurosurgeon at a civilian partnered location with their previous volume at a military treatment facility and analyzed current trends in wartime readiness by Neurosurgery Knowledge, Skills and Abilities metrics. We believe that military civilian partnerships hold the key to scaffolding the experience to maintain the wartime readiness in the military neurosurgical community.


Mucoepidermoid carcinoma of uterine cervix stage IB. Long-term follow-up, histochemical and immunohistochemical study.
Twelve women with mucoepidermoid carcinoma of the cervix uteri were followed for 2-15 years after diagnosis. Three patients died within 14 months. All had lymph node metastases and/or vascular involvement and exhibited tumor invasion to a depth of 1.2-3.2 cm. Mucoepidermoid carcinoma is defined as a tumor with the appearance of squamous cell carcinoma without any glandular pattern and with demonstrable intracellular mucin. The mucin is best demonstrated by alcian blue and periodic acid-Schiff-diastase. In 265 cases of squamous cell carcinoma, stage IB, lymph node metastases were present in 14%. In the cases of mucoepidermoid carcinoma, the prevalence of nodal metastases was 33%. Because mucoepidermoid carcinomas appear to be more aggressive lesions than squamous cell carcinomas are, it may be advisable to stain all cervical squamous carcinomas for mucin if they demonstrate finely vacuolated cytoplasm and lack peripheral palisading. Immunohistochemical studies for carcinoembryonic antigen (CEA), keratin, and epithelial membrane antigen were positive in all tumors to varying degrees. The detection of CEA may be of additional help in establishing a diagnosis.


Photocatalytic Anatase TiO2 Thin Films on Polymer Optical Fiber Using Atmospheric-Pressure Plasma.
Due to the undeniable industrial advantages of low-temperature atmospheric-pressure plasma processes, such as low cost, low temperature, easy implementation, and in-line process capabilities, they have become the most promising next-generation candidate system for replacing thermal chemical vapor deposition or wet chemical processes for the deposition of functional coatings. In the work detailed in this article, photocatalytic anatase TiO2 thin films were deposited at a low temperature on polymer optical fibers using an atmospheric-pressure plasma process. This method overcomes the challenge of forming crystalline transition metal oxide coatings on polymer substrates by using a dry and up-scalable method. The careful selection of the plasma source and the titanium precursor, i.e., titanium ethoxide with a short alkoxy group, allowed the deposition of well-adherent, dense, and crystalline TiO2 coatings at low substrate temperature. Raman and XRD investigations showed that the addition of oxygen to the precursor's carrier gas resulted in a further increase of the film's crystallinity. Furthermore, the films deposited in the presence of oxygen exhibited a better photocatalytic activity toward methylene blue degradation assumedly due to their higher amount of photoactive {101} facets.


A chymotrypsin-like serine protease interacts with the chitin synthase from the midgut of the tobacco hornworm.
The chitin portion of the peritrophic matrix in the midgut of the tobacco hornworm, Manduca sexta, is produced by chitin synthase 2 (CHS2), a transmembrane family II glycosyltransferase, located at the apical tips of brush border microvilli. To look for proteins that potentially interact with CHS2, we performed yeast two-hybrid screening, identifying a novel chymotrypsin-like protease (CTLP1) that binds to the extracellular carboxyterminal domain of CHS2. The occurrence of this interaction in vivo is supported by co-localization and co-immunoprecipitation data. Based on our findings we propose that chitin synthesis is controlled by an intestinal proteolytic signalling cascade linking chitin synthase activity to the nutritional state of the larvae.


Perinatal and childhood risk factors for later criminality and violence in schizophrenia. Longitudinal, population-based study.
Individuals with schizophrenia appear to be at increased risk for violent and criminal behaviour. Obstetric complications, neuromotor problems and intellectual deficits have variously been reported as increasing the risk for criminality in the general population. To investigate whether such risk factors are associated with criminal behaviour in an epidemiological cohort of patients with schizophrenia. We identified from health care registers all individuals with schizophrenia born in Helsinki between 1951 and 1960, and used the national criminal register to identify those with a criminal record by 1995. Childhood information was obtained from archived birth and school records. Poor educational attainment, poor grades for attention at school, higher birth weight and larger head circumference were significantly associated with the risk of criminal offending in adulthood in this sample of patients with schizophrenia. An association between labour/delivery complications and later violent offending among male patients was of borderline significance. Our hypotheses that birth complications and childhood neuromotor problems would increase the risk of criminal offending in schizophrenia were not upheld.


Current concepts on gingival fibromatosis-related syndromes.
Gingival fibromatosis is a rare, benign, slowly-growing fibrous overgrowth of the gingiva, with great genetic and clinical heterogeneity. Gingival fibromatosis/overgrowth can be inherited as an isolated trait (hereditary gingival fibromatosis) and/or as a component of a syndrome, or it can be drug induced. As a clinical manifestation of a syndrome, gingival fibromatosis is usually associated with generalized hypertrichosis, mental retardation, or epilepsy. Gingival fibromatosis and its related syndromes are mainly inherited in an autosomal-dominant manner, but autosomal-recessive inheritance has also been reported. Clinical syndromic presentation includes Zimmermann-Laband syndrome, Ramon syndrome, Rutherford syndrome, Cowden syndrome, Cross syndrome, Göhlich-Ratmann syndrome, Avani syndrome, and I-cell disease. However, a phenotypic overlap has been suggested, as many combinations of their systemic manifestations have been reported. Treatment of choice is usually gingivectomy with gingivoplasty. Before any therapy, clinical practitioners must take into consideration the clinical course of a particular syndrome and every possible functional and esthetic disorder.


'We just do the dirty work': dealing with incontinence, courtesy stigma and the low occupational status of carework in long-term aged care facilities.
To systematically examine, describe and explain how continence care was determined, delivered and communicated in Australian long aged care facilities. Incontinence is a highly stigmatising condition that affects a disproportionally large number of people living in long-term aged care facilities. Its day-to-day management is mainly undertaken by careworkers. We conducted a Grounded theory study to explore how continence care was determined, delivered and communicated in long-term aged care facilities. This paper presents one finding, i.e. how careworkers in long-term aged care facilities deal with the stigma, devaluation and the aesthetically unpleasant aspects of their work. Grounded theory. Eighty-eight hours of field observations in two long-term aged care facilities in Australia. In addition, in-depth interviews with 18 nurses and careworkers who had experience of providing, supervising or assessment of continence care in any long-term aged care facility in Australia. Occupational exposure to incontinence contributes to the low occupational status of carework in long-term aged care facilities, and continence care is a symbolic marker for inequalities within the facility, the nursing profession and society at large. Careworkers' affective and behavioural responses are characterised by: (1) accommodating the context; (2) dissociating oneself; (3) distancing oneself and (4) attempting to elevate one's role status. The theory extends current understandings about the links between incontinence, continence care, courtesy stigma, emotional labour and the low occupational status of carework in long-term aged care facilities. This study provides insights into the ways in which tacit beliefs and values about incontinence, cleanliness and contamination may affect the social organisation and delivery of care in long-term aged care facilities. Nurse leaders should challenge the stigma and devaluation of carework and careworkers, and reframe carework as 'dignity work'.


A Perspective on the Trends and Challenges Facing Porphyrin-Based Anti-Microbial Materials.
The emergence of multidrug resistant bacterium threatens to unravel global healthcare systems, built up over centuries of medical research and development. Current antibiotics have little resistance against this onslaught as bacterium strains can quickly evolve effective defense mechanisms. Fortunately, alternative therapies exist and, at the forefront of research lays the photodynamic inhibition approach mediated by porphyrin based photosensitizers. This review will focus on the development of various porphyrins compounds and their incorporation as small molecules, into polymers, fibers and thin films as practical therapeutic agents, utilizing photodynamic therapy to inhibit a wide spectrum of bacterium. The use of photodynamic therapy of these porphyrin molecules are discussed and evaluated according to their electronic and bulk material effect on different bacterium strains. This review also provides an insight into the general direction and challenges facing porphyrins and derivatives as full-fledged therapeutic agents and what needs to be further done in order to be bestowed their rightful and equal status in modern medicine, similar to the very first antibiotic; penicillin itself. It is hoped that, with this perspective, new paradigms and strategies in the application of porphyrins and derivatives will progressively flourish and lead to advances against disease.


Effects of non-pharmacological interventions on ventricular late potentials.
The purpose of the paper is to review the presently available information of the effects of non-pharmacological interventions for the control of drug-refractory ventricular tachyarrhythmias on non-invasively recorded ventricular late potentials. During recent years, non-pharmacological interventions have evolved as an alternative form of treatment to control drug-refractory ventricular tachyarrhythmias. The effects of these non-pharmacological measures on ventricular late potentials are poorly understood. Successful surgical control of ventricular tachycardia often normalizes the signal averaged ECG and may eliminate delayed potentials. Thus, this non-invasive test may be useful in assessing surgical efficacy in subgroups of patients with ventricular tachycardia. However, the clinical value of late potentials in assessing surgical efficacy in the individual case may be limited as the sensitivity and specificity of the loss of late potentials after antitachycardia surgery are low. In addition, the effects of transvenous catheter ablation on ventricular late potentials will be reviewed. The available information suggests that this intervention has little effects on the presence or absence of late potentials. Thus, non-invasive recording of late potentials seems not to be helpful in predicting the acute and long-term efficacy of catheter ablation. In conclusion, changing of the parameters in the signal-averaged QRS complex after antitachycardia surgery may be useful in predicting the efficacy of surgical interventions for drug-refractory ventricular tachycardias in subgroups of patients. However, the sensitivity and predictive accuracy of this test are low, thus limiting its clinical usefulness.


Dectin-1 interaction with tetraspanin CD37 inhibits IL-6 production.
C-type lectins are pattern-recognition receptors important for pathogen binding and uptake by APCs. Evidence is accumulating that integration of incoming cellular signals in APCs is regulated by grouping of receptors and signaling molecules into organized membrane complexes, such as lipid rafts and tetraspanin microdomains. In this study, we demonstrate that C-type lectin dectin-1 functionally interacts with leukocyte-specific tetraspanin CD37. Dectin-1 and CD37 colocalize on the surface of human APCs. Importantly, macrophages of CD37-deficient (CD37(-/-)) mice express decreased dectin-1 membrane levels, due to increased dectin-1 internalization. Furthermore, transfection of CD37 into a macrophage cell line elevated endogenous dectin-1 surface expression. Although CD37 deficiency does not affect dectin-1-mediated phagocytosis, we observed a striking 10-fold increase of dectin-1-induced IL-6 production in CD37(-/-) macrophages compared with wild-type cells, despite reduced dectin-1 cell surface expression. Importantly, the observed increase in IL-6 production was specific for dectin-1, because signaling via other pattern-recognition receptors was unaffected in CD37(-/-) macrophages and because the dectin-1 ligand curdlan was used. Taken together, these findings show that tetraspanin CD37 is important for dectin-1 stabilization in APC membranes and controls dectin-1-mediated IL-6 production.


[A Marginal Case of Malaria: An Interesting Malaria Story of Cameroon Origin].
Malaria is a serious, contagious infection caused by single-celled parasites. About 200 species of Plasmodium have been described that can cause infection in vertebrates. Five different species of Plasmodium are known to cause infection in humans to date. Infection with more than one type of pathogen is called coinfection. This type of infections can be caused by different species of the same genus, as well as by different species. Malaria coinfections are mostly caused by the combination of Plasmodium vivax and Plasmodium falciparum. In this study, a case of malaria admitted to the hospital and diagnosed was presented. Thin smear blood preparations were prepared from the peripheral blood of a 54 year-old Republic of Türkiye citizen male patient who applied to the emergency department with fever and chills. The preparations were stained with Giemsa and examined under a microscope with a x 100 objective, and trophozoite and gametocyte forms belonging to Plasmodium genus were determined. As a result of probe-based quantitative real-time polymerase chain reaction (qRt-PCR) study with primers specific to Plasmodium vivax, Plasmodium malariae, Plasmodium falciparum, Plasmodium ovale and Plasmodium knowlesi for definitive species identification, co-infection of P.vivax, P.falciparum, P.ovale and P.knowlesi was detected in the patient. In addition, it was proved that our patient was infected with four different species by conventional PCR study in which five species were studied and then by DNA sequence analysis. On the fourth day of artemether-lumefantrine treatment, the patient's fever response was observed and the trophozoite forms disappeared from the third day in the daily peripheral smear follow-up. Since P.vivax and P.ovale species were also detected after species determination by molecular methods, primaquine 1 x 30 mg tablet was added to the existing drugs for the treatment of hypnozoite forms of the parasite. In recent years, there has been an increase in malaria imported cases, especially after visits to African countries. Such rare cases of malaria coinfection may be encountered during visits to geographies located at the intersection of endemic regions. According to the data of the World Health Organization, maximum attention should be paid to the prevention and prophylaxis protocols from vectors, especially in travels to countries with the highest mortality and morbidity. In co-infection cases similar to our patient, for tertian malaria and tertiary ovale malaria, hypnozoid therapy should not be overlooked. When the insecticide-resistant vectors and drug-resistant Plasmodium strains encountered in recent years are evaluated as a whole, there is a need to develop more effective strategies in the fight against malaria. In addition to microscopic examination, which is accepted as the gold standard, we believe that evaluating molecular studies together in diagnosis is extremely important for the treatment process when hypnozoite periods are considered.


PENet-a scalable deep-learning model for automated diagnosis of pulmonary embolism using volumetric CT imaging.
Pulmonary embolism (PE) is a life-threatening clinical problem and computed tomography pulmonary angiography (CTPA) is the gold standard for diagnosis. Prompt diagnosis and immediate treatment are critical to avoid high morbidity and mortality rates, yet PE remains among the diagnoses most frequently missed or delayed. In this study, we developed a deep learning model-PENet, to automatically detect PE on volumetric CTPA scans as an end-to-end solution for this purpose. The PENet is a 77-layer 3D convolutional neural network (CNN) pretrained on the Kinetics-600 dataset and fine-tuned on a retrospective CTPA dataset collected from a single academic institution. The PENet model performance was evaluated in detecting PE on data from two different institutions: one as a hold-out dataset from the same institution as the training data and a second collected from an external institution to evaluate model generalizability to an unrelated population dataset. PENet achieved an AUROC of 0.84 [0.82-0.87] on detecting PE on the hold out internal test set and 0.85 [0.81-0.88] on external dataset. PENet also outperformed current state-of-the-art 3D CNN models. The results represent successful application of an end-to-end 3D CNN model for the complex task of PE diagnosis without requiring computationally intensive and time consuming preprocessing and demonstrates sustained performance on data from an external institution. Our model could be applied as a triage tool to automatically identify clinically important PEs allowing for prioritization for diagnostic radiology interpretation and improved care pathways via more efficient diagnosis.


Lysophosphatidic Acid Mediates Activating Transcription Factor 3 Expression Which Is a Target for Post-Transcriptional Silencing by miR-30c-2-3p.
Although microRNAs (miRNAs) are small, non-protein-coding entities, they have important roles in post-transcriptional regulation of most of the human genome. These small entities generate fine-tuning adjustments in the expression of mRNA, which can mildly or massively affect the abundance of proteins. Previously, we found that the expression of miR-30c-2-3p is induced by lysophosphatidic acid and has an important role in the regulation of cell proliferation in ovarian cancer cells. The goal here is to confirm that ATF3 mRNA is a target of miR-30c-2-3p silencing, thereby further establishing the functional role of miR-30c-2-3p. Using a combination of bioinformatics, qRT-PCR, immunoblotting and luciferase assays, we uncovered a regulatory pathway between miR-30c-2-3p and the expression of the transcription factor, ATF3. Lysophosphatidic acids triggers the expression of both miR-30c-2-3p and ATF3, which peak at 1 h and are absent 8 h post stimulation in SKOV-3 and OVCAR-3 serous ovarian cancer cells. The 3´-untranslated region (3´-UTR) of ATF3 was a predicted, putative target for miR-30c-2-3p, which we confirmed as a bona-fide interaction using a luciferase reporter assay. Specific mutations introduced into the predicted site of interaction between miR-30c-2-3p and the 3´-UTR of ATF3 alleviated the suppression of the luciferase signal. Furthermore, the presence of anti-miR-30c-2-3p enhanced ATF3 mRNA and protein after lysophosphatidic acid stimulation. Thus, the data suggest that after the expression of ATF3 and miR-30c-2-3p are elicited by lysophosphatidic acid, subsequently miR-30c-2-3p negatively regulates the expression of ATF3 through post-transcriptional silencing, which prevents further ATF3-related outcomes as a consequence of lysophosphatidic acid signaling.


[Microbiological, pharmacokinetic and clinical studies of rokitamycin dry syrup in the pediatric field].
Rokitamycin (RKM), a newly developed macrolide antibiotic with a 16-membered ring, dissolves well under acidic conditions. It has been improved over other macrolides to minimize individual variations in its absorbability. We measured, using the GA-test, variations in gastric acidities of 43 children with ages between 1 to 14 years, and investigated the relationship between gastric acidities and pharmacokinetic values. Also activities (expressed in MICs) of antimicrobial agents were studied against clinically isolated 229 bacterial strains using an inoculum size of 10(6) cells/ml. Tested organisms included Streptococcus pyogenes (77 strains), Streptococcus agalactiae (29), Streptococcus pneumoniae (2), as Gram-positive cocci, and Haemophilus influenzae (1), Haemophilus parainfluenzae (1), Bordetella pertussis (12), Salmonella sp. (4) and Campylobacter jejuni (103) as Gram-negative bacilli. Against stock strains of bacteria, MICs of 10 drugs (RKM, erythromycin (EM), josamycin (JM), midecamycin (MDM), midecamycin acetate (MOM), clindamycin (CLDM), amoxicillin (AMPC), cefaclor (CCL), minocycline, ofloxacin (OFLX] were determined. Against isolates from patients who underwent treatment with RKM, MICs of only 4 drugs (RKM, EM, JM, MOM) were determined. Measurements were made on plasma and urinary concentrations of RKM and its urinary recovery rates after patients including 6 boys with ages between 5 years 1 month and 11 years 6 months were administered with RKM (dry syrup). Two groups of 6 boys were administered between meals with RKM at dose levels of 5 and 10 mg/kg, respectively. Clinical and bacteriological effects of RKM were evaluated for 175 patients including 5 cases of pharyngitis, 3 tonsillitis, 32 pneumonia, 17 mycoplasmal pneumonia, 34 atypical pneumonia, 28 streptococcal infections, 29 Campylobacter enteritis, 4 Salmonella gastroenteritis, and 23 enteritis due to unknown organisms. Five drop-out cases were excluded from the evaluations. In the evaluable cases, an average dose level used was 31.8 mg/kg/day, with a daily dose divided into 3 to 4 administrations and with an average treatment duration of 9 days. Adverse reactions of RKM and its effects on laboratory test values were investigated in these patients including the drop out cases. Obtained results of these studies are summarized below. 1. The GA-test produced pH values indicating that amounts of gastric acid were mostly either normal or high in 42 of the 43 subjects tested (97.7%), and only one low acid case (2.3%) was observed.(ABSTRACT TRUNCATED AT 400 WORDS)


Is there an association between clinical presentation and the location and extent of myocardial involvement of cardiac sarcoidosis as assessed by ¹⁸F- fluorodoexyglucose positron emission tomography?
Positron emission tomography using (18)F-Fluorodeoxyglucose (FDG) is an emerging modality for diagnosis of cardiac sarcoidosis (CS). We compared the location and degree of FDG uptake in CS patients presenting with either advanced atrioventricular block (AVB) or ventricular tachycardia (VT). We included consecutive patients who presented with either AVB or VT with a diagnosis of CS. A cohort of patients with clinically silent CS was included as controls. FDG activity was quantified as standardized uptake values (SUV) and both the overall mean left ventricular (LV) SUV as well as the Maximum Mean Segmental SUV was recorded for each patient. Receiver operator characteristic (ROC) analysis was performed to identify cutoff SUV values that best identified patients with VT. A total of 27 patients with CS were included (13 females; mean age, 56 ± 8 years; 8 VT, 12 AVB, and 7 controls). Both mean LV SUV and Max SUV in CS patients presenting with VT were significantly higher compared with those with AVB (mean SUV: VT median 5.33, range 4.7-9.35 versus AVB median 2.48, range 0.86-8.59, P=0.016; max SUV: VT median 11.07, range 9.24-14.4 versus AVB median 5.63, range 3.42-15.71, P=0.005) and compared with controls. There was no significant difference in SUV values between AVB patients and controls. ROC analysis for identification of patients with VT showed AUCs of 0.93 and 0.895 for a mean LV SUV of >3.42 and a max SUV >8.56, respectively (P<0.001). CS patients with VT displayed significantly higher FDG uptake when compared with those with AVB and asymptomatic controls. Further prospective studies are required to evaluate this finding.


Atypical clinical presentation of distal renal tubular acidosis: a case report registered in Amazonas, Brazil.
We report an unusual case of a 24-year-old girl with a history of recurrent hypokalemic paralysis episodes and skin lesions on the lower limbs and buttocks, both of which had an acute evolution. In subsequent investigations, the patient also had nephrocalcinosis, nephrolithiasis, hyperchloremic metabolic acidosis and persistent alkaline urinary pH. The findings were consistent with distal renal tubular acidosis as the cause of hypokalemic paralysis. Clinical findings, immunological tests and the result of skin biopsy suggested primary Sjögren's syndrome as an underlying cause. The patient developed azotemia due to obstructive nephrolithiasis. All the features presented in this case are an unusual manifestation of distal renal tubular acidosis; so far, we are not aware of a similar report in the literature.


[Interrelations between serum folic acid and hematologic changes in psychiatric patients].
Changes in the blood picture as well as in the content of folic acid and iron in the serum were investigated in 223 patients treated in a psychiatric clinic because of psychoses and dementia. Psychopharmaka of the phenobarbiturate type, dihydrophenytoine as well as primidone were administered in 29 cases. As anaemia could be identified in 32 patients; 3 of them turned out to be a hyperchronic anaemia, 25 a normochromic anaemia and 4 a hypochromic type one. In 78.1% of the anaemic patients there was a lowered folic acid level. All four cases with hypochromic anaemia showed a lowered serum level. A hypersegmentation of neutrophilic granulocytes could be identified in 48 patients (28.4%), with a lowered folic acid content in the serum being present in all cases. A lowered folic acid content in the serum could be found in 76.2% of the patients. All patients treated with psychopharmaka showed a subnormal folic acid content. On the other hand, a lowered iron content in the serum could only be identified in 8.1% of the cases. The final evaluation of all findings gathered results in the recommendation to attach greater importance to a direct determination of folic acid concentration in the serum in those cases of disease particularly exposed.


Some aspects of complementarity in the immune system. A bird's eye view.
The burden of this paper is the suggestion that the defence capacity of the immune system is rather limited. It cannot stand in readiness to deal with a practically endless diversity and abundance of microbes. In contrast to conventional thinking the current model proposes: (1) The core idea that cells of the immune system are basically and constantly interconnected with host cells (e.g., through TCR-MHC interactions) and that foreign antigens (peptides) may tend to obstruct such interactions. Peptides presented during a viral infection typically decrease complementarity between the structures that are the products of the major histocompatibility complex (MHC) genes (or other genes related to it) and T cells. The altered MHC profile exposes infected cells to a polyclonal immune attack from other T cells such that tissue destruction occurs in an allograft rejection-like fashion. This may explain why a substantial portion of T cell numbers is activated when only a small number of specific T cells is 'obstructed' from functioning by the presence of nonself peptides. (2) Phagocytes 'see' targets even in a non-immune host because complement distribution associated with polyreactive natural antibodies magnifies sensitization differences between pathogens and host cells. (3) There is only a probability that hypermutation will successfully change the genome in some B cell clones to produce high affinity antibodies that prevent the re-infection of the host by the same pathogen, but cannot conquer primary infections. (4) The history of the development of the immune responses suggests that during prolonged interaction between host and microbes in our natural habitat, carried on over many generations, the adaptive antibody population may facilitate the evolution of the natural antibody repertoire. The model predicts that microbes, which are not a part of the local environment, may invade the organism without significant resistance. The model is discussed in various interactions for survival in the context of infection and tumorigenicity.


Collective backscattering of gyrotron radiation by small-scale plasma density fluctuations in large helical device.
A version of the collective backscattering diagnostic using gyrotron radiation for small-scale turbulence is described. The diagnostic is used to measure small-scale (k(s) approximately 34 cm(-1)) plasma density fluctuations in large helical device experiments on the electron cyclotron heating of plasma with the use of 200 kW 82.7 GHz heating gyrotron. A good signal to noise ratio during plasma production phase was obtained, while contamination of stray light increased during plasma build-up phase. The effect of the stray radiation was investigated. The available quasioptical system of the heating system was utilized for this purpose.


Expression and purification of GST-FHL2 fusion protein.
Escherichia coli is the most widely used host for the production of recombinant proteins. However, most eukaryotic proteins are typically obtained as insoluble, misfolded inclusion bodies that need solubilization and refolding. The interactions between human FHL2 protein and many types of proteins, including structural proteins, kinases, and several classes of transcription factor, have been found to have important roles in a variety of fundamental processes, including arrhythmia, hypertrophy, atherosclerosis, and angiogenesis. To achieve high-level expression of soluble recombinant human FHL2 protein in E. coli, we have constructed a recombinant expression plasmid, pGEX-4T-1-FHL2, in which we merged FHL2 cDNA with the glutathione S-transferase (GST) coding sequence downstream of the tac inducible promoter. Using this plasmid, we have achieved high expression of soluble FHL2 as a GST fusion protein in E. coli BL21. We have used the engineered plasmid (pGEX-4T-1-FHL2) and the modified E. coli strain to overcome the problem of removing the GST moiety while expressing soluble FHL2. Our results show that: 1) the recombinant plasmid was successfully constructed. Sequencing results showed that FHL2 and GST are in the same reading frame; 2) at 23°C, soluble GST-FHL2 fusion protein was highly expressed after induction with 0.1 mM IPTG; and 3) GST-FHL2 can be detected by Western blotting using mouse monoclonal anti-GST antibody. Our data are the first to show that high yields of soluble FHL2 tagged with GST can be achieved in E.coli.


Rectal inflammatory myofibroblastic tumor: Case report and literature review.
Rectal inflammatory myofibroblastic tumor (IMT) is an extremely rare mesenchymal tumor characterized by a mixture of spindle-shaped myofibroblasts or fibroblasts and inflammatory infiltration of lymphocytes and plasma cells. To date, only 8 cases of rectal IMT have been reported. Herein, we report an additional case of rectal IMT in a 28-year-old woman. A 28-year-old woman presented with abdominal pain and hematochezia. Colonoscopy showed a 3.0-cm subepithelial tumor with central ulceration, covered by white exudate in the rectum. Rectal magnetic resonance imaging revealed a 4.0 × 3.0-cm-sized well-defined subepithelial tumor in the right wall of the rectum, with suspicious right perirectal fat infiltration. Laparoscopic anterior resection was performed. Microscopic examination of the surgical specimen revealed bland-looking spindle cells intermingled with lymphoplasma cells. Immunohistochemistry and fluorescence in situ hybridization showed anaplastic lymphoma kinase positivity and anaplastic lymphoma kinase positivity rearrangement. Rectal IMT was confirmed based on histological, immunohistochemical, and fluorescence in situ hybridization findings. The patient was doing well without evidence of tumor recurrence 1 year after the surgery. Rectal IMT, despite its rarity, should be considered in the differential diagnosis of rectal cancer. Second, an accurate histopathologic diagnosis and complete surgical resection can be the most important approaches to offer a chance for the cure of rectal IMT.


Tumor necrosis factor receptor-associated factor family protein 2 is a key mediator of the epidermal growth factor-induced ribosomal S6 kinase 2/cAMP-responsive element-binding protein/Fos protein signaling pathway.
TRAF2 has an important function in mediating the TNF-R signaling pathway toward activation of NF-κB and JNKs. Here we reveal a novel function of TRAF2 in the epidermal growth factor (EGF) signaling pathway. Knockdown of TRAF2 blocked EGF-induced AP-1 activity and anchorage- independent cell transformation. Notably, we showed that EGF induces ribosomal S6 kinase 2 (RSK2) ubiquitination, and knocking down TRAF2 suppresses ubiquitination of RSK2 induced by EGF. We also found that TRAF2 affects RSK2 activity through RSK2 ubiquitination. RSK2 plays a critical role in AP-1 activity mediated through CREB and c-Fos, which regulates anchorage-independent cell transformation. In addition, TRAF2 is overexpressed in colon cancer and required for colon cancer development, suggesting that TRAF2 might be a potential molecular target for cancer prevention and treatment.


High-throughput metagenomic analysis of petroleum-contaminated soil microbiome reveals the versatility in xenobiotic aromatics metabolism.
The soil with petroleum contamination is one of the most studied soil ecosystems due to its rich microorganisms for hydrocarbon degradation and broad applications in bioremediation. However, our understanding of the genomic properties and functional traits of the soil microbiome is limited. In this study, we used high-throughput metagenomic sequencing to comprehensively study the microbial community from petroleum-contaminated soils near Tianjin Dagang oilfield in eastern China. The analysis reveals that the soil metagenome is characterized by high level of community diversity and metabolic versatility. The metageome community is predominated by γ-Proteobacteria and α-Proteobacteria, which are key players for petroleum hydrocarbon degradation. The functional study demonstrates over-represented enzyme groups and pathways involved in degradation of a broad set of xenobiotic aromatic compounds, including toluene, xylene, chlorobenzoate, aminobenzoate, DDT, methylnaphthalene, and bisphenol. A composite metabolic network is proposed for the identified pathways, thus consolidating our identification of the pathways. The overall data demonstrated the great potential of the studied soil microbiome in the xenobiotic aromatics degradation. The results not only establish a rich reservoir for novel enzyme discovery but also provide putative applications in bioremediation.


Integrating hierarchical bioavailability and population distribution into potential eco-risk assessment of heavy metals in road dust: A case study in Xiandao District, Changsha city, China.
Modified eco-risk assessment method (MEAM) integrated with the hierarchical bioavailability determined by the fraction detection of Cd, Pb, Zn, Cu, Cr in road dust samples and the local population distribution derived from the local land use map, was proposed to make the hierarchical eco-risk management strategy in Xiandao District (XDD), China. The geo-accumulation index (Igeo), the original potential eco-risk index (Er(i)) and the modified eco-risk assessment index (MEAI) were used to identify the priority pollutant. Compared with the Hunan soil background values, evaluated metal concentrations were found to different extent. The results of mean Igeo, Er(i) and bioavailability of studied metals revealed the following orders: Cd>Pb ≈ Zn>Cu ≈ Cr, Cd>Pb>Cu>Cr>Zn and Cd>Zn>Cu ≈ Pb>Cr, respectively. Therefore, Cd was regarded as the priority pollutant. To identify the priority areas taking into account cost consideration, the hierarchical risk map based on the results of the modified eco-risk assessment index with overlay of the population density map was needed and made. The west and partly south areas of XDD were under higher eco-risk generally. Moreover, the whole XDD area was divided into 4 area categories with different management priorities based on the possibility of occurrence of eco-risk, and the hierarchical risk management strategy associated with protecting local population was suggested to facilitate allocation of funds for risk management.


Splice variant IVS2-2A>G in the SLC26A5 (Prestin) gene in five Estonian families with hearing loss.
The aim of our study was to identify the IVS2-2A>G sequence change in the SLC26A5 (Prestin) gene in Estonian individuals with hearing loss and in their family members. In the years 2005-2007 we have screened 194 probands with early onset hearing loss and 68 family members with an arrayed primer extension (APEX) microarray, which covers 201 mutations in six nuclear genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5) and two mitochondrial genes encoding 12S rRNA and tRNA-Ser (UCN). In four probands with early onset hearing loss and in five unaffected family members from five families we identified the IVS2-2A>G change in one allele of the SLC26A5 gene. We did not find any homozygosity for this splice variant. IVS2-2A>G was identified in 2.1% of probands. One of these probands, however, is also homozygous for the 35delG mutation in the GJB2 gene and a second patient has Down syndrome, which is also associated with hearing impairment. Therefore, in those two cases the etiology of the hearing loss is probably not associated with the IVS2-2A>G sequence change in the SLC26A5 gene. Our data support the hypothesis that heterozygosity for the mutation IVS2-2A>G in SLC26A5 gene may not, by itself, be sufficient to cause hearing loss.


High-Velocity Quadriceps Exercises Compared to Slow-Velocity Quadriceps Exercises Following Total Knee Arthroplasty: A Randomized Clinical Study.
Despite improvement in pain and perceived function in older adults following total knee arthroplasty (TKA), objective outcome measures of muscular impairment and ambulatory function demonstrate significant deficits. Evidence suggests that quadriceps power may play a greater role in ambulatory function than measures of strength alone following TKA. The purpose of this study was to compare the effect of high-velocity (HV) quadriceps exercises with that of slow-velocity (SV) quadriceps exercises on functional outcomes and quadriceps power following TKA. This study was a randomized clinical study conducted in an outpatient physical therapy clinic. Twenty-one participants who were 4 to 6 weeks post unilateral TKA were randomly assigned to an HV or SV group. Participants performed an evidence-based standardized progressive resistance exercise program in addition to HV quadriceps exercises or SV quadriceps exercises. Participants attended 2 sessions per week for 8 weeks. Before and after the 8-week exercise intervention, participants completed a functional questionnaire, health survey, functional testing, and underwent quadriceps strength and power testing. Both groups demonstrated improvements in ambulatory outcome measures, strength, speed, and power. The HV group demonstrated significantly greater improvements in distance walked and quadriceps strength than the SV group. These data should be considered preliminary because of a small sample size. HV quadriceps exercises may be an effective rehabilitation strategy in conjunction with a standardized progressive resistance exercise program beginning 4 to 6 weeks after TKA.


Development of phenotypic and genotypic resistance to antiretroviral therapy in the UNAIDS HIV Drug Access Initiative--Uganda.
We describe phenotypic drug resistance, response to therapy, and genotypic mutations among HIV-infected patients in Uganda taking antiretroviral medications for > or = 90 days who had a viral load > or = 1000 copies/ml. HIV-1 group and subtype, virologic and immunologic responses to antiretroviral therapy, phenotypic resistance to antiretroviral drugs, and associated genotypic mutations among patients at three treatment centers in Uganda between June 1999 and August 2000 were assessed. Therapy was two nucleoside reverse transcriptase inhibitors (NRTIs) or highly active antiretroviral therapy (HAART). All HIV identified was HIV-1, group M, subtypes A, C, and D. Sixty-one (65%) of 94 patients with a phenotypic resistance result had evidence of phenotypic resistance including resistance to a NRTI for 51 of 92 (55%) taking NRTIs, to a non-nucleoside reverse transcriptase inhibitor (NNRTI) for nine of 16 (56%) taking NNRTIs, and to a protease inhibitor (PI) for eight of 37 (22%) taking PIs. At the time of the first specimen with resistance, the median change from baseline viral load was -0.56 log copies/ml [interquartile range (IQR), -1.47 to +0.29] and CD4+ cell count was +35 x 10(6) cells/l (IQR, -18 to +87). Genotypic resistance mutations, matched with phenotypic resistance assay results and drug history, were generally consistent with those seen for HIV-1, group M, subtype B infections in industrialized countries. Initial phenotypic resistance and corresponding genotypic mutations among patients treated in Uganda were similar to those with subtype B infections in North America and Europe. These data support policies that promote the use of HAART regimens against HIV-1, group M, non-B subtypes in a manner consistent with that used for subtype B infections.


Lysosomal Degradation Is Required for Sustained Phagocytosis of Bacteria by Macrophages.
Clearance of bacteria by macrophages involves internalization of the microorganisms into phagosomes, which are then delivered to endolysosomes for enzymatic degradation. These spatiotemporally segregated processes are not known to be functionally coupled. Here, we show that lysosomal degradation of bacteria sustains phagocytic uptake. In Drosophila and mammalian macrophages, lysosomal dysfunction due to loss of the endolysosomal Cl- transporter ClC-b/CLCN7 delayed degradation of internalized bacteria. Unexpectedly, defective lysosomal degradation of bacteria also attenuated further phagocytosis, resulting in elevated bacterial load. Exogenous application of bacterial peptidoglycans restored phagocytic uptake in the lysosomal degradation-defective mutants via a pathway requiring cytosolic pattern recognition receptors and NF-κB. Mammalian macrophages that are unable to degrade internalized bacteria also exhibit compromised NF-κB activation. Our findings reveal a role for phagolysosomal degradation in activating an evolutionarily conserved signaling cascade, which ensures that continuous uptake of bacteria is preceded by lysosomal degradation of microbes.


Excited State Resonance Raman of Flavin Mononucleotide: Comparison of Theory and Experiment.
Blue light absorbing flavoproteins play important roles in a variety of photobiological processes. Consequently, there have been numerous investigations of their excited state structure and dynamics, in particular by time-resolved vibrational spectroscopy. The isoalloxazine chromophore of the flavoprotein cofactors has been studied in detail by time-resolved Raman, lending it a benchmark status for mode assignments in excited electronic states of large molecules. However, detailed comparisons of calculated and measured spectra have proven challenging, as there are many more modes calculated than are observed, and the role of resonance enhancement is difficult to characterize in excited electronic states. Here we employ a recently developed approach due to Elles and co-workers ( J. Phys. Chem. A 2018, 122, 8308-8319) for the calculation of resonance-enhanced Raman spectra of excited states and apply it to the lowest singlet and triplet excited states of the isoalloxazine chromophore. There is generally good agreement between calculated and observed enhancements, which allows assignment of vibrational bands of the flavoprotein cofactors to be refined. However, some prominently enhanced bands are found to be absent from the calculations, suggesting the need for further development of the theory.


A single orally administered dose of almitrine improves pulmonary gas exchange during exercise in patients with chronic air-flow obstruction.
To verify if the improvement in gas exchange observed at rest with almitrine in patients with chronic air-flow obstruction is maintained at exercise, we studied 10 patients on a randomized, crossover, double-blind exercise protocol. After assessment of steady state of their disease, patients with FEV 1 less than 1.5 L.s-1 and PaCO2 less than 70 mmHg cycled 8 to 11 min at 80% of their previously determined maximal O2 uptake. Blood gases, arterial lactate (La), expired ventilation, (VE), O2 uptake (Vo2), Co2 production (VCO2), heart rate (HR), and arterial blood pressure (BP) were measured at rest, at mid-exercise, at end-exercise, and at 2, 14, 15, and 35 min of recovery. We found that at all stages of the study PaO2 was significantly higher in those who had received almitrine than in those who had received placebo; the mean increment was 11.9 torr at rest, 8.9 at end-exercise, and 13.7 at 15 min of recovery. Changes in PaCO2 and arterial (H+) were the opposite of those in PaO2; at end-exercise PaCO2 was 5.9 torr lower in those who had received almitrine, and pH was 7.36 versus 7.32 in those who had received placebo. No significant difference was found at all stages of the study between drug and placebo with respect to VE, VO2, VCO2, HR, and BP. But the ventilatory equivalent for oxygen, VE/VO2, was slightly higher in those who had received almitrine than in those who had received placebo during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)


Mental health and vitality among Canadian women with physical disabilities.
This study investigated scores for mental health and vitality in a large community-based sample of women with physical disabilities. The scores from two subscales of the SF-36 were collected from 1,096 women with physical disabilities through a mailed survey regarding health and well-being. These scores were compared to normative data using t tests. The mean scores of the vitality subscale were significantly lower than that of the normed sample when analyzed by age groups. The mental health scores were significantly lower as well, except for one age group (65-74 yr.). These results suggest that health care workers should address aspects of mental health and energy when caring for women with physical disabilities, as these areas are often overlooked in this population. Health promotion programs aimed at these topics should be designed specifically for this population as well.


In vitro curing of persistent infection of HVJ (sendai virus) carrier tumor cells by spleen cells.
The viral antigens of hamster tumor cells persistently infected with HVJ (Sendai virus) disappeared upon transplantation, showing that HVJ persistent infection can be cured in vivo. In order to analyze these phenomena, an attempt to achieve a similar cure in vitro was made. When HVJ carrier tumor cells (GM2-HVJpi) were cultured in the presence of sera from GM2-HVJpi- tumor-bearing hamsters or rabbit antiserum against glycoproteins (GP) of HVJ, the cells showed only weak stainability with fluorescent antibody (FA). Lymphokines produced by spleen cells from GM2-HVJpi-tumor bearers could not cause GM2-HVJpi cells to lose their viral antigens. However, the viral antigens of GM2-HVJpi cells became undetectable upon cocultivation with spleen cells from either normal of GM2-HVJpi tumor-bearing hamsters. These cells from which HVJ antigens had been lost were reconfirmed to be cured in vitro through single colony isolation and subsequent establishment of a new HVJ infection after superinfection of the isolated cells with HVJ. The above results indicate that the curing of virus persistent infections in HVJ carrier tumor cells by transplantation was due to the in vivo action of spleen cells against transplanted HVJ carrier tumor cells.


High brain serotonin levels in migraine between attacks: A 5-HT4 receptor binding PET study.
Migraine has been hypothesized to be a syndrome of chronic low serotonin (5-HT) levels, but investigations of brain 5-HT levels have given equivocal results. Here, we used positron emission tomography (PET) imaging of the 5-HT4 receptor as a proxy for brain 5-HT levels. Given that the 5-HT4 receptor is inversely related to brain 5-HT levels, we hypothesized that between attacks migraine patients would have higher 5-HT4 receptor binding compared to controls. Eighteen migraine patients without aura (migraine free >48 h), and 16 age- and sex-matched controls underwent PET scans after injection of [11C]SB207145, a specific 5-HT4 receptor radioligand. An investigator blinded to group calculated a neocortical mean [11C]SB207145 binding potential (BPND). Three migraine patients reported a migraine attack within 48 h after the scan and were excluded from the primary analysis. Comparing 15 migraine patients and 16 controls, we found that migraine patients have significantly lower neocortical 5-HT4 receptor binding than controls (0.60 ± 0.09 vs. 0.67 ± 0.05, p = .024), corrected for 5-HTTLPR genotype, sex and age. We found no association between 5-HT4 receptor binding and attack frequency, years with migraine or time since last migraine attack. Our finding of lower 5-HT4 receptor binding in migraine patients is suggestive of higher brain 5-HT levels. This is in contrast with the current belief that migraine is associated with low brain 5-HT levels. High brain 5-HT levels may represent a trait of the migraine brain or it could be a consequence of migraine attacks.


Screening genes that change expression during compression wood formation in Chamaecyparis obtusa.
We screened cDNA fragments that change their expression during compression wood formation by fluorescent differential display (FDD) in five adult trees (Chamaecyparis obtusa (Siebold & Zucc.) Endl.) growing naturally at an angle to the vertical, and in two saplings, one vertical, the other inclined. We conducted anatomical observations and measurements of the released strain of growth stress on the five adult trees to confirm that they formed compression wood on the lower side of the inclined trunks. Based on sequencing results from selected cDNA fragments, we conducted homology searches of the GenBank database and designed specific primers for the 67 screened fragments. Using these primers and different saplings from those used for the FDD screening, we tested the expression levels of each fragment in normal, compression and opposite wood regions of saplings by semiquantitative reverse-transcription polymerase chain reaction. Twenty-four fragments showed reproducible expression patterns, indicating that these fragments changed their expression during compression wood formation. Some fragments showed differential expression between the apical and basal regions of the lower side of the inclined stem in the region of compression wood formation. Anatomical observations indicated more intense compression wood formation in the basal region than in the apical region of the stem, demonstrating a relationship between compression wood development and gene expression.


Modulation by food restriction of intracellular calcium signaling in parotid acinar cells of aging Fischer 344 rats.
Previous studies suggest that alpha 1-adrenergic (alpha 1-AR)-induced intracellular calcium ([Ca2+]i) mobilization in rat parotid acinar cells declines with age. In this study, we examined the effects of food restriction on alpha 1-AR and muscarinic-stimulated [Ca2+]i mobilization in parotid acinar cells during aging. [Ca2+]i levels in response to the alpha 1-AR agonist epinephrine and the muscarinic agonist carbachol were evaluated in Fura-2-loaded parotid acinar cells from ad libitum-fed (AL) and food-restricted (FR) Fischer 344 male rats at 4, 6, 14, and 24 months of age. [Ca2+]i responses to epinephrine and carbachol (10 microM) were significantly reduced (48% and 35%, respectively; p < .05) in cells from 24-month-old AL rats as compared to younger AL rats. In contrast, no significant reduction of epinephrine and carbachol responses was observed in 24-month-old FR animals. An age-related increase in basal [Ca2+]i (peak around 14 months; p < .02) was observed in both AL and FR rats. In addition, basal [Ca2+]i was higher in FR than in AL rats at 14 and 24 months of age (p < .02). These studies suggest that FR partially attenuates or delays age-related impairments in alpha 1-AR- and muscarinic-cholinergic signal transduction systems of parotid acinar cells. Basal [Ca2+]i also appears to be altered during aging and by FR.


Awake videolaryngoscopic orotracheal intubation in patients with laryngeal tumour using the C-MAC D-Blade.
This study assessed the applicability of C-MAC videolaryngoscope (VL) D-blade for awake intubation in patients with laryngeal tumour. The primary study objective was to determine the rate of successful intubation in the first attempt. The other parameters recorded were number of attempts required for intubation, duration of different stages of intubation, haemodynamics, ease of intubation and patient comfort on visual analogue scale (VAS) postoperatively. Thirty patients were studied. Patients were sedated with dexmedetomidine and fentanyl as a slow bolus (over 20 min) and Ramsay sedation score was assessed. Topicalisation of the oropharynx, tonsillar pillars and base of the tongue was done with lignocaine 10% spray. Four ml of 4% lignocaine using MADgic atomiser was used for anaesthetising the glottis and the tracheal lumen. Successful intubation was achieved in 86.6% patients in first attempt and 13.3% in two attempts. Total time for all intubations was less than 30 seconds. Fremantle score was F-1-C-MAC D-blade (easy intubation with full view) in 60% patients, while 23.3% had F-2-C-MAC D-blade (full view and either required more than one attempt or a modified technique), 13.3% had P-1-C-MAC D-blade (partial view with easy intubation) and 3.3% had P-2-C-MAC D-blade (partial view and required more than one attempt or a modified technique). The VAS score for anaesthesiologist's ease and for patient's experience was 85.83 ± 7.20 and 86.66 ± 14.46, respectively. C-MAC VL D-blade-assisted awake intubation is an effective and safe method to manage the airway of patients with laryngeal tumour once adequate topicalisation is ensured before the procedure.


["The ludicrous judgement" by Boileau, Gui Patin and the Academy of Lamoignon].
L'Arrêt burlesque (The ludicrous judgement) by Boileau (1671) is a most striking work of satire with relation to medicine and literature. The circumstances of its composition call to mind the atmosphere prevailing at that time in the home of the famous magistrate Guillaume de Lamoignon, where Doctor Gui Patin and Later Nicolas Boileau were so warmly welcomed and greatly favoured.


Mucosal adjuvants.
The vast majority of pathogens invade the body through or establish infections in the mucosal tissues. Development of vaccines to combat mucosal infections represents a top priority. Mucosal immunization has recently attracted much interest as a means of generating protective immunity against mucosal pathogens. Conversely, only very few mucosal vaccines are presently approved for human use. The development of a broad range of mucosal vaccines will necessitate the development of safe and effective mucosal adjuvants and delivery systems. Over the past decade, a number of immunomodulatory agents, including toxin based adjuvants, Toll like receptor (TLR) mimetics and non TLR-targeting immunostimulators as well as delivery systems have shown promise for mucosal administration in experimental animals. However, their possible use in humans remains to be established. This paper attempts to provide a brief overview of the mucosal immunization and adjuvants with an emphasis on mucosal adjuvants in or close to clinic.